Integrative Bioinformatics Links HNF1B with Clear Cell Carcinoma and Tumor-Associated Thrombosis

• DOI: 10.1371/journal.pone.0074562
• Publication Date: 2013-09-09T22:35:56Z
• Authors: Justin Cuff; Keyan Salari; Nicole Clarke; Ghada E. Esheba; Andrew D. Forster; Stephanie Huang; Robert B. West; John P. Higgins; Teri A. Longacre; Jonathan R. Pollack
• Keywords: HNF1B; Tissue microarray; Hepatocyte nuclear factors; Clear cell carcinoma

Clear cell carcinoma (CCC) is a histologically distinct subtype that arises in several organ systems and marked by cytoplasmic clearing, attributed to abundant intracellular glycogen. Previously, transcription factor hepatocyte nuclear 1-beta (HNF1B) was identified as biomarker of ovarian CCC. Here, we set out explore more broadly the relation between HNF1B carcinomas with clear histology. expression, evaluated immunohistochemistry, significantly associated histology across diverse gynecologic renal (P<0.001), hypomethylation promoter (P<0.001). From microarray analysis, an empirically-derived signature enriched for computationally-predicted targets (with HNF1 binding sites) (P<0.03), well genes glycogen metabolism, including glucose-6-phophatase, strikingly blood clotting cascade, fibrinogen, prothrombin XIII. Enrichment cascade also evident data from CCC versus other histotypes (P<0.01), HNF1B-associated expression verified immunohistochemistry (P = 0.015). Finally, among immunostaining linked 3.0-fold increased risk clinically-significant venous thrombosis 0.043), 2.3-fold 0.011) combined cohort. Our results define broad marker phenotype, support mechanistic link accumulation thrombosis, possibly reflecting (for CCC) derivation secretory endometrium. findings implicate novel mechanism tumor-associated (a major cause cancer mortality), based on direct production factors cells.